Ontologies, Mental Disorders and Prototypes

As it emerged from philosophical analyses and cognitive research, most concepts exhibit typicality effects, and resist to the efforts of defining them in terms of necessary and sufficient conditions. This holds also in the case of many medical concepts. This is a problem for the design of computer science ontologies, since knowledge representation formalisms commonly adopted in this field do not allow for the representation of concepts in terms of typical traits. However, the need of representing concepts in terms of typical traits concerns almost every domain of real world knowledge, including medical domains. In particular, in this article we take into account the domain of mental disorders, starting from the DSM-5 descriptions of some specific mental disorders. On this respect, we favor a hybrid approach to the representation of psychiatric concepts, in which ontology oriented formalisms are combined to a geometric representation of knowledge based on conceptual spaces

The involvement of replication in single stranded oligonucleotide-mediated gene repair

Targeted gene repair mediated by single-stranded oligonucleotides (SSOs) has great potential for use in functional genomic studies and gene therapy. Genetic changes have been created using this approach in a number of prokaryotic and eukaryotic systems, including mouse embryonic stem cells. However, the underlying mechanisms remain to be fully established. In one of the current models, the ‘annealing-integration’ model, the SSO anneals to its target locus at the replication fork, serving as a primer for subsequent DNA synthesis mediated by the host replication machinery. Using a λ-Red recombination-based system in the bacterium Escherichia coli, we systematically examined several fundamental premises that form the mechanistic basis of this model. Our results provide direct evidence strongly suggesting that SSO-mediated gene repair is mechanistically linked to the process of DNA replication, and most likely involves a replication intermediate. These findings will help guide future experiments involving SSO-mediated gene repair in mammalian and prokaryotic cells, and suggest several mechanisms by which the efficiencies may be reliably and substantially increased

Нарушения в геноме хозяина при экспериментальном гименолепидозе в зависимости от дозы введенного инвазивного материала при заряжении

ГИМЕНОЛЕПИДО

Subtle gene modification in mouse ES cells: evidence for incorporation of unmodified oligonucleotides without induction of DNA damage

Gene targeting by single-stranded oligodeoxyribonucleotides (ssODNs) is a promising tool for site-specific gene modification in mouse embryonic stem cells (ESCs). We have developed an ESC line carrying a mutant EGFP reporter gene to monitor gene correction events shortly after exposure to ssODNs. We used this system to compare the appearance and fate of cells corrected by sense or anti-sense ssODNs. The slower appearance of green fluorescent cells with sense ssODNs as compared to anti-sense ssODNs is consistent with physical incorporation of the ssODN into the genome. Thus, the supremacy of anti-sense ssODNs, previously reported by others, may be an artefact of early readout of the EGFP reporter. Importantly, gene correction by unmodified ssODNs only mildly affected the viability of targeted cells and did not induce genomic DNA double-stranded breaks (DSBs). In contrast, ssODNs that were end-protected by phosphorothioate (PTO) linkages caused increased H2AX phosphorylation and impaired cell cycle progression in both corrected and non-corrected cells due to induction of genomic DSBs. Our results demonstrate that the use of unmodified rather than PTO end-protected ssODNs allows stable gene modification without compromising the genomic integrity of the cell, which is crucial for application of ssODN-mediated gene targeting in (embryonic) stem cells

Start-to-end Transport Design and Multi-particle Tracking for the ILC Electron Source

A train of 2-ns micro bunches of longitudinally polarized electrons are generated in a 120-kV DC-gun based injector in the ILC electron source; a bunching system with extremely high bunching efficiency to compress the micro-bunch down to 20 ps FWHM is designed. Complete optics to transport the electron bunch to the entrance of the 5-GeV damping ring injection line is developed. Start-to-end multi-particle tracking through the beamline is performed including the bunching system, pre-acceleration, chicane, 5-GeV superconducting booster linac, spin rotators and energy compressor. It shows that 94% of the electrons from the DC-gun are captured within the damping ring 6-D acceptance--A{sub x} + A{sub y} {le} 0.09 m and {Delta}E x {Delta}z {le} ({+-} 25 MeV) x ({+-} 3.46 cm)--at the entrance of the damping ring injection line. The field and alignment errors and orbit correction are analyzed

Insulin Glargine in the Intensive Care Unit: A Model-Based Clinical Trial Design

Online 4 Oct 2012Introduction: Current succesful AGC (Accurate Glycemic Control) protocols require extra clinical effort and are impractical in less acute wards where patients are still susceptible to stress-induced hyperglycemia. Long-acting insulin Glargine has the potential to be used in a low effort controller. However, potential variability in efficacy and length of action, prevent direct in-hospital use in an AGC framework for less acute wards. Method: Clinically validated virtual trials based on data from stable ICU patients from the SPRINT cohort who would be transferred to such an approach are used to develop a 24-hour AGC protocol robust to different Glargine potencies (1.0x, 1.5x and 2.0x regular insulin) and initial dose sizes (dose = total insulin over prior 12, 18 and 24 hours). Glycemic control in this period is provided only by varying nutritional inputs. Performance is assessed as %BG in the 4.0-8.0mmol/L band and safety by %BG<4.0mmol/L. Results: The final protocol consisted of Glargine bolus size equal to insulin over the previous 18 hours. Compared to SPRINT there was a 6.9% - 9.5% absolute decrease in mild hypoglycemia (%BG<4.0mmol/L) and up to a 6.2% increase in %BG between 4.0 and 8.0mmol/L. When the efficacy is known (1.5x assumed) there were reductions of: 27% BG measurements, 59% insulin boluses, 67% nutrition changes, and 6.3% absolute in mild hypoglycemia. Conclusion: A robust 24-48 clinical trial has been designed to safely investigate the efficacy and kinetics of Glargine as a first step towards developing a Glargine-based protocol for less acute wards. Ensuring robustness to variability in Glargine efficacy significantly affects the performance and safety that can be obtained

Collaboration Between Public Health and Law Enforcement: New Paradigms and Partnerships for Bioterrorism Planning and Response

The biological attacks with powders containing Bacillus anthracis sent through the mail during September and October 2001 led to unprecedented public health and law enforcement investigations, which involved thousands of investigators from federal, state, and local agencies. Following recognition of the first cases of anthrax in Florida in early October 2001, investigators from Centers for Disease Control and Prevention (CDC) and the Federal Bureau of Investigation (FBI) were mobilized to assist investigators from state and local public health and law enforcement agencies. Although public health and criminal investigations have been conducted in concert in the past, the response to the anthrax attacks required close collaboration because of the immediate and ongoing threat to public safety. We describe the collaborations between CDC and FBI during the investigation of the 2001 anthrax attacks and highlight the challenges and successes of public health and law enforcement collaborations in general

Engaging Citizen Scientists to Keep Transit Times Fresh and Ensure the Efficient Use of Transiting Exoplanet Characterization Missions

This white paper advocates for the creation of a community-wide program to maintain precise mid-transit times of exoplanets that would likely be targeted by future platforms. Given the sheer number of targets that will require careful monitoring between now and the launch of the next generation of exoplanet characterization missions, this network will initially be devised as a citizen science project -- focused on the numerous amateur astronomers, small universities and community colleges and high schools that have access to modest sized telescopes and off-the-shelf CCDs.Comment: White Paper submitted to Astro2020 Science Call, 5 pages, 3 figures, community comments and involvement are welcome